RADIATION/HYPERTHERMIA THERAPY FOR CHORIDAL MELANOMA
脉络膜黑色素瘤的放射/热疗
基本信息
- 批准号:3265103
- 负责人:
- 金额:$ 18.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1990
- 资助国家:美国
- 起止时间:1990-04-01 至 1994-03-31
- 项目状态:已结题
- 来源:
- 关键词:combination cancer therapy cytotoxicity disease /disorder model dosage electroretinography eye disorder diagnosis eye neoplasms fluorescein angiography histopathology human therapy evaluation laboratory rabbit neoplasm /cancer radiation therapy neoplasm /cancer thermotherapy nonhuman therapy evaluation radiation immunosuppression radiation therapy dosage radiobiology radiotracer xenotransplantation
项目摘要
Malignant choroidal melanoma is the most common primary intraocular
neoplasm in adults. For over 100 years, enucleation was the accepted
treatment for this disease. The ideal treatment, however, would eradicate
the tumor while preserving ocular function. Recent suggestions that
enucleation may, in fact, promote the development of distant metastases has
led to the use of limited surgical techniques which preserve the eye.
Radiation therapy has replaced enucleation as the most common treatment,
and is now the subject of a nation-wide clinical trial (Collaborative
Ocular Melanoma Study). Unfortunately, the potential advantages of
radiation therapy can be negated by the development of chronic radiation-
induced complications, particularly in the treatment of tumors grater than
8mm height. The secondary complications eventually impair ocular function
and may result in loss of the eye.
The use of hyperthermia (42o to 45o C) in combination with radiation has
been demonstrated to enhance the effectiveness of radiation therapy in the
treatment of human cutaneous melanomas by a factor of two. In an animal
model of Greene choroidal melanoma, the combination of these modalities has
been demonstrated to allow a reduction of radiation dose while maintaining
tumor control. We expect that reducing the radiation dose will lead to
fewer secondary complications, thereby preserving useful vision.
We have established a new xenograft model of human choroidal melanoma in
immuno-suppressed rabbit eyes which we expect to behave more like human
choroidal melanoma in situ than the older Greene model. In addition, we
have developed a new clinical technique for combining hyperthermia produced
by 500 KHz radiofrequency current with I125 irradiation using a gold
episcleral plaque. A Phase-1 clinical evaluation of this technique is
currently in progress at our institution. We have developed quantitative
I125 dosimetry for our plaque delivery system, and preliminary hyperthermia
dosimetry in normal rabbit eyes. We have demonstrated that the normal
rabbit eye can tolerate temperatures up to 45oC, measured at the plaque-
sclera interface, with tolerable acute toxicity.
We proposed to: 1) develop quantitative hyperthermia dosimetry for our
heating technique in rabbit eyes containing the human uveal melanoma
xenograft; 2) determine the dose-response relationship for our xenograft
model to I125 irradiation alone; 3) determine the "dose" temperature
response for the xenograft model to hyperthermia alone; 4) determine the
dose-response of the xenograft model to the combined modalities, and 5)
assess acute chronic toxicity following treatment with irradiation,
hyperthermia, or the combined modalities and doses associated with tumor
control. Due to the lack of a fovea in the rabbit eye, we further propose
to evaluate acute toxicity (from the combined modalities) in a limited
number of primate eyes if results using the rabbit model disclose a
potential therapeutic gain.
恶性脉络膜黑色素瘤是最常见的原发性眼内
成人肿瘤。 100多年来,眼球摘除术
治疗这种疾病。 然而,理想的治疗方法是
同时保留眼部功能。 最近的建议,
事实上,眼球摘除可能促进远处转移的发展,
导致使用有限的手术技术来保护眼睛。
放射疗法已经取代眼球摘除术成为最常见的治疗方法,
现在是一个全国性的临床试验的主题(合作
眼黑色素瘤研究)。 不幸的是,
放射治疗可能会被慢性放射的发展所否定,
引起的并发症,特别是在治疗肿瘤大于
8 mm高。 继发性并发症最终损害眼功能
并可能导致眼睛丧失。
高温疗法(42 °至45 ° C)与放射疗法相结合,
已被证明可以提高放射治疗的有效性,
治疗人类皮肤黑色素瘤的两倍。 动物中
格林脉络膜黑色素瘤模型,这些方式的组合,
已被证明可以减少辐射剂量,同时保持
肿瘤控制 我们预计减少辐射剂量将导致
更少的继发性并发症,从而保留有用的视力。
我们建立了一种新的人脉络膜黑色素瘤异种移植模型,
免疫抑制的兔眼,我们希望它的行为更像人类
原位脉络膜黑色素瘤的发生率高于较老的格林模型。 另外我们
开发了一种新的临床技术,
通过500 KHz射频电流与I125照射,使用金
巩膜外斑 该技术的1期临床评价是
目前正在进行中。 我们开发了定量的
用于我们的斑块输送系统的I125剂量测定和初步热疗
正常兔眼的剂量测定。 我们已经证明了正常的
兔眼可以耐受高达45摄氏度的温度,在斑块处测量-
巩膜界面,急性毒性可耐受。
我们建议:1)发展定量热疗剂量学,
兔眼葡萄膜黑色素瘤的热处理技术
异种移植物; 2)确定我们的异种移植物的剂量-反应关系
3)确定“剂量”温度
异种移植物模型对单独的热疗的反应; 4)确定
异种移植物模型对联合模式的剂量反应,以及5)
评估辐照处理后的急性和慢性毒性,
热疗,或与肿瘤相关的联合方式和剂量
控制 由于兔眼缺乏中央凹,我们进一步建议
在有限的条件下评价急性毒性(来自组合模式),
如果使用兔子模型的结果显示
潜在的治疗增益。
项目成果
期刊论文数量(0)
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